Project Summary Cryptosporidiosis is a leading contributor to child morbidity and mortality worldwide, responsible for over 200,000 deaths in children under two, and morbidity in over 7 million children. However, we have limited treatment and no vaccine for use in young children. Our prior work in Bangladesh has demonstrated that almost 80% of children in an urban slum cohort were infected with Cryptosporidium spp. and that infection, even without diarrhea, was significantly associated with long-term growth faltering. Cryptosporidiosis is spread by fecal oral contamination. We observed in a pilot transmission study in urban Bangladesh that households with one Cryptosporidium infected child, had a 30% secondary attack rate in other family members, and some affected family members carried the same Cryptosporidium genotype. In contrast, households with Cryptosporidium negative children had no secondary infections among other family members. We propose to establish a longitudinal cohort of families with young children (< 1 year of age) in urban Bangladesh to determine risk factors for person-to- person transmission. Specifically, we aim to understand how host level characteristics, including nutritional status and gut microbiota, and parasite genetic diversity impact risk of household transmission and pathogenicity of disease. This proposal leverages a longstanding collaboration between Johns Hopkins University, University of Virginia, and the International Centre for Diarrhoeal Disease, Research, Bangladesh. This proposal is innovative, as it will be the first large household transmission study of cryptosporidiosis to identify transmission to a sub-species level, and correlate this with measures disease severity and risk factors for transmission. The findings from this study will inform interventional efforts aimed to protect young children from this devastating infectious disease.